1. Field of the Invention
The invention is generally related to a psychotherapeutic use for the natural product vanillin and derivatives of vanillin.
2. Description of the Prior Art
Vanillin has the chemical name 4-hydroxy-3-methoxybenzaldehyde and the chemical structure: ##STR1## Vanillin occurs naturally in vanilla beans, potato parings, and Siam benzoin, and is produced synthetically from eugenol or guaiacol or from the lignin waste from the wood pulp industry.
Vanillin is relatively nontoxic; the Merck index reports an oral LD.sub.50 for vanillin of 1580 mg/kg in rats. The relative safety of vanillin is further borne out by the fact that it was given GRAS (i.e., "generally regarded as safe") status by the Flavor and Extract Manufacturer's Association (FEMA) and was recognized for food use by the Food and Drug Administration (FDA). In man, vanillin is converted to vanillic acid in the liver and is excreted in the urine.
The vanillin compound is devoid of nitrogen, unlike many of the conventionally-prescribed tranquilizer and/or sedative compounds, such as the family of drugs known as benzodiazepines. The benzodiazepines include diazepam (e.g., such as marketed under the brand name "Valium") and chlordiazepoxide (e.g., such as marketed under the brand name "Librium"), and they are central nervous system (CNS) depressants. These benzodiazepines are generally effective for relief of symptoms of anxiety, tension, fatigue or agitation and present a low risk of lethality in humans when taken alone (e.g., diazepam has an oral LD.sub.50 of 1240 mg/kg in rats). They nonetheless can have serious adverse side effects. For instance, known reported side effects of these benzodiazepines include the fact that they can be abused if taken for extended periods of time; also withdrawal symptoms can occur upon discontinuance of the therapy; they are subject to certain drug interaction concerns; and they may cause birth defects in first trimester fetuses, and/or make the fetus dependent upon the drug, and they can even be transmitted from a medicated mother to newborn infants through breast milk. Therefore, there are certain serious risks associated with administering benzodiazepines to women of child-bearing age, in particular, unless an appropriate prior investigation is made before they are administered to this class of patients.
By contrast, vanillin is commonly used in relatively trivial concentrations as a flavoring agent in confectionery, beverages, foods, tobacco; and as a scent in perfumery. The highest average national level of use reported is 768 ppm, in confectionaries and frostings, and possible average daily intake of vanillin from foods has been estimated as 38.9 mg/capita, as reported by the National Technical Information Service, US Dept. of Commerce, Springfield, Va. 22161, Report fda/bf-78/157 Scientific Literature Review of Vanillin and Derivatives in Flavor Usage, August 1978, p 4.
Vanillin also has been used in trivial amounts for the limited purpose of flavoring dosage forms of pharmaceutically active agents to encourage patient acceptance. For example, U.S. Pat. No. 4,267,185 (Finizio) describes benzenobenzisoquinoline derivatives useful as antidepressants that can be administered, among other ways, in the form of a suspension flavored with a relatively small amount of vanillin. Similarly, U.S. Pat. No. 4,351,836 (Rajagopalan) describes pyrrolylpiperidines useful as antidepressants that can administered, among other ways, in the form of a suspension flavored with a very small amount of vanillin. Also, the use of vanillin as a flavorant for dosages of (amidomethyl)nitrogen heterocyclic and pyrrolidine compounds used for analgesics, diuretics, and so forth, is described in U.S. Pat. No. 5,254,569 (Cheeseman et al.). Similarly, U.S. Pat. No. 5,043,350 (Pennev et al.) discloses vanillin as a flavorant for doses of benzo-fused cycloalkane and oza- and thia-cycloalkane trans-1,2-diamine compounds useful as analgesics and/or diuretics. The optional use of vanillin as a flavorant for an electrolyte stabilizing composition used for detoxifying chronic alcoholics and hard-line drug addicts while avoiding major withdrawal symptoms is mentioned in U.S. Pat. No. 4,582,705 (Primes et al.).
An actual medicinal use of vanillin for the limited purpose of treating of sickle cell anemia, a blood disorder, has been reported by D. Abraham, et al., "Vanillin, a Potential Agent for the Treatment of Sickle Cell Anemia," Blood, Vol. 77, No. 6 (March 15) 1991: pp. 1334-1341.
However, there is an unsatisfied need in the prior art of psychotherapy for a central nervous system (CNS) depressant agent that poses less risk of adverse side effects and other pernicious effects to the host.